Laura K. Bachrach

Acquisition of optimal bone mass in childhood and adolescence

Peak bone mass (PBM), which is achieved by early adulthood, is a key determinant of the lifetime risk of osteoporosis. Because the foundation for skeletal health is established so early in life, osteoporosis prevention begins by optimizing gains in bone mineral throughout childhood and adolescence. Heritable factors account for an estimated 60-80% of the variability in PBM, with diet, physical activity and hormonal status serving as important modifiers of bone accrual. Recent pediatric studies have clarified the tempo and magnitude of gains in bone mineral and the modulating effects of diet, activity and sex steroids. The challenge lies in designing effective means to reverse trends of decreased calcium consumption, increased sodium intake and diminished physical activity among children and adolescents. Equally important is raising the awareness of health care providers to recognize children at risk for suboptimal acquisition of PBM.

Disordered eating, menstrual irregularity, and Bone minéral Density in Female runners

PURPOSE To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. METHODS Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. RESULTS An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. CONCLUSION In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

Clinical Review: Bisphosphonate Use in Childhood Osteoporosis

CONTEXT As awareness of osteoporosis in childhood has increased, so have pressures to consider use of the pharmacological agents used to treat osteoporosis in adults. This review examines available research on the efficacy and safety of bisphosphonate therapy for pediatric osteoporosis. EVIDENCE ACQUISITION We reviewed the medical literature for key articles and consensus statements on the use of bisphosphonates in children through June 2008. EVIDENCE SYNTHESIS We compared reports using varying bisphosphonate agents, doses, and duration of therapy to treat osteogenesis imperfecta and a variety of secondary causes of osteoporosis in children. Conclusions drawn from a recently published Cochrane analysis and the consensus statements from experts in the field were considered as well. CONCLUSIONS Use of bisphosphonate therapy in pediatric patients remains controversial because of inadequate long-term efficacy and safety data. For this reason, many experts recommend limiting use of these agents to those children with recurrent extremity fractures, symptomatic vertebral collapse, and reduced bone mass. Current data are inadequate to support the use of bisphosphonates in children to treat reductions in bone mass/density alone. More research is needed to define appropriate indications for bisphosphonate therapy and the optimal agent, dose, and duration of use in pediatric patients.

Bone mass and hip axis length in healthy Asian, Black, Hispanic, and white American youths

The primary objective of this study was to examine the associations of ethnicity, diet (calcium, protein, energy), and weight‐bearing activity with dual‐energy X‐ray absorptiometry (DXA)‐measured bone mass and hip axis length (HAL) in 423 Asians, blacks, Hispanics, and non‐Hispanic Caucasians, aged 9–25 years. Bone mass was expressed as bone mineral content (BMC), bone mineral density (BMD), and bone mineral apparent density (BMAD). The data were analyzed using multiple linear regression, after stratifying for gender and pubertal stage and adjusting for height and weight. With few exceptions, Asians and Hispanics had comparable bone mass to whites at all pubertal stages. Greater femoral neck BMAD in black than white females was observed at all pubertal stages. Black males displayed greater BMD and BMAD than white males at all sites in early puberty and at the femoral neck in maturity. Calcium was positively and protein negatively related to BMAD at the femoral neck in early pubertal females. Among males, calcium was negatively associated with whole body BMC and BMD and spine BMD and BMAD in midpuberty. Weight‐bearing activity was not associated with bone mass in females; in males, it was positively related only to femoral neck BMC in early puberty. There was an absence of evidence for ethnic differences in HAL among females. In males, we observed shorter HAL in mature Asians and blacks than whites. Neither diet nor activity was associated with HAL.

Bone acquisition and loss in children and adults with cystic fibrosis: A longitudinal study☆☆☆★★★

OBJECTIVES To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD). STUDY DESIGN Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD. RESULTS Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score. CONCLUSIONS Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.

Osteopenia in adults with cystic fibrosis

PURPOSE To examine the frequency and severity of osteopenia in adults with cystic fibrosis and the clinical variables associated with reduced bone mineral. PATIENTS AND METHODS The bone mineral status of 22 white adults (14 women) with cystic fibrosis was compared with normative data from healthy white control subjects in a university medical center. Lumbar spine, femoral neck, and whole-body bone mineral was determined by dual energy x-ray absorptiometry and expressed as bone mineral content (g), bone mineral density (g/cm2), and bone mineral apparent density (g/cm3). Bone mass was related to age, body mass, gonadal function, pulmonary status, and glucocorticoid exposure to identify variables associated with reduced bone mineral in cystic fibrosis. RESULTS Bone mineral in adults with cystic fibrosis was significantly below expected values for age and sex at all sites using all expressions of bone mass. The mean Z-score was -2.8 for the lumbar spine bone density, -2.5 for the femoral neck, and -2.0 for the whole body. Bone mineral apparent density (a term that minimizes the influence of bone dimensions) was also significantly reduced in patients at the lumbar spine (p < 0.0001) and femoral neck (p < 0.001 to p < 0.0001), indicating that the bone mineral deficit seen in adults with cystic fibrosis could not be attributed to differences in bone size. Age, weight, height, and body mass index were significantly correlated with bone mineral. Pulmonary status, glucocorticoid use, and gonadal function failed to predict bone mineral status. CONCLUSIONS Osteopenia and osteoporosis occur commonly in young adults with cystic fibrosis. Age and body mass are predictive of bone mineral, although the pathogenesis of this bone mineral deficit is likely multifactorial.

Low bone mineral density at axial and appendicular sites in amenorrheic athletes.

Amenorrheic athletes have low axial bone-mineral density (BMD, g.cm-2). We compared 12 amenorrheic and 9 eumenorrheic women athletes to determine whether athletes with amenorrhea have lower BMD in other skeletal regions, including weight-bearing lower limbs. BMD was measured by dual energy x-ray and single photon absorptiometry. Both groups had similar age, body mass, and exercise quantity. Women with amenorrhea missed 86.3 +/- 58.3 menstrual periods since menarche. BMD was lower in the amenorrheic vs eumenorrheic subjects for the lumbar spine (0.928 +/- 0.056 vs 1.050 +/- 0.110, P < 0.005), whole body (1.032 +/- 0.05 vs 1.09 +/- 0.06, P < 0.05), most regions of the whole body (P < 0.05-0.001), all areas of the proximal femur (P < 0.005), and at the femoral mid-shaft (1.333 +/- 0.109 vs 1.491 +/- 0.088, P < 0.005). No significant differences were detected at the mid-radius and tibial shaft. The best predictors of BMD were years of regular menstruation for lumbar spine; and years of amenorrhea for hip, femoral mid-shaft, and whole body. We conclude that low BMD in athletes with amenorrhea is not limited to the axial skeleton but is also present in other regions including appendicular weight-bearing bones.

The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture.

The effects of three putative growth factors and serum on [Me-3H]thymidine and Na125I incorporation into thyroid cell cultures have been examined. We found that serum and EGF could stimulate radioactively labelled thymidine incorporation into confluent cultures. However, both factors completely inhibited iodine uptake and organification at low concentrations. Insulin also stimulated [Me-3H]thymidine incorporation but had no adverse effect on thyroid differentiated function. TSH examined under the same conditions was not a growth factor but was essential to maintain differentiated functions. We conclude that thyroid growth and differentiation are not mutually exclusive processes. However, EGF and serum inhibit thyroid differentiated function at very low concentrations. Elucidation of the physiological role of these factors and their mechanism of action may lead to a greater understanding of thyroid hormone biosynthesis.

Clinical Report—Bone Densitometry in Children and Adolescents

Concern for bone fragility in children and adolescents has led to increased interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve the expected gains in bone size, mass, and strength, which leaves them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less certain. This clinical report summarizes the current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and its risks and costs. This report emphasizes consensus statements generated at the 2007 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, and others reflect expert opinion, because the available data are inadequate. The statements from this and other expert panels have provided general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. Ongoing studies will help to better define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk.

Bone Mineral, Histomorphometry, and Body Composition in Adults with Growth Hormone Receptor Deficiency

Growth hormone (GH) and insulin‐like growth factor I (IGF‐I) deficiencies have been associated with osteopenia in both children and adults. To examine the effects of growth hormone resistance on bone mineral and body composition, we studied 11 adults (mean age 30 years) with growth hormone receptor deficiency (GHRD, Laron syndrome) and 11 age‐ and gender‐matched controls from Southern Ecuador. Bone mineral and body composition were determined by dual‐energy X‐ray absorptiometry. Bone physiology was assessed with biochemical markers of bone turnover and dynamic bone histomorphometry. Bone size and body composition differed markedly between subjects with GHRD and controls. Affected adults were 40 cm shorter than controls, had significantly less lean body mass, and had increased percent body fat. Bone mineral content and density (BMD) at the spine, femoral neck, and whole body were significantly lower in adults with GHRD than in controls. Mean BMD Z scores were −1.5 to −1.6 at all sites in affected women and −2.2 to −2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 ± 0.025 versus 0.177 ± 0.021 for affected women versus controls (p < 0.05) and 0.173 ± 0.018 versus 0.191 ± 0.025 for men with GHRD versus normals (p = 0.31). Urinary pyridinoline concentrations were significantly greater in adults with GHRD than in controls, while type I collagen C‐telopeptide breakdown products and markers of bone formation did not differ. Differences in histomorphometry were limited to a reduction in trabecular connectivity; bone volume and formation rate were similar to controls. These data confirm the importance of the GH/IGF axis in regulating bone size and body composition. The contribution of these peptides to the acquisition and maintenance of bone mineral is less certain since volumetric bone density was preserved despite low levels of IGF‐I and IGFBP‐3 associated with GH resistance.